bHLH转录因子TCF4的亚细胞定位是由多个核定位和核输出信号介导的。,Scientific Reports

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bHLH转录因子TCF4的亚细胞定位是由多个核定位和核输出信号介导的。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-10-30 , DOI: 10.1038/s41598-019-52239-w
Beata Greb-Markiewicz ₁ , Wioletta Kazana _{1,

2} , Mirosław Zarębski ₃ , Andrzej Ożyhar ₁

Affiliation

转录因子4（TCF4）是I类基本螺旋-环-螺旋（bHLH）转录因子，可调节细胞的神经发生和特异性。TCF4在免疫系统的发育和功能中也起着重要作用。另外，TCF4调节支持细胞和桥脑核神经元的发育，肌生成，黑色素生成和上皮-间质转化。转录因子完成其功能的能力通常取决于它们在细胞核与细胞质之间的细胞内运输。贩运受到特定序列的控制，即核定位信号（NLS）和核输出信号（NES）。我们通过对可能充当NLS或NES的基序进行定位和详细表征，对TCF4运输调控序列进行了研究。我们证明TCF4的bHLH域包含一个与两个NES重叠的NLS。计算机分析的结果表明，序列的高度保守性，特别是在NLS和NESs区域。这种高度保守性不仅在小鼠和人类TCF4之间，而且在TCF4与其他哺乳动物E蛋白之间，表明这些序列对于bHLH I类转录因子的功能至关重要。

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The subcellular localization of bHLH transcription factor TCF4 is mediated by multiple nuclear localization and nuclear export signals.

Transcription factor 4 (TCF4) is a class I basic helix-loop-helix (bHLH) transcription factor which regulates the neurogenesis and specialization of cells. TCF4 also plays an important role in the development and functioning of the immune system. Additionally, TCF4 regulates the development of Sertoli cells and pontine nucleus neurons, myogenesis, melanogenesis and epithelial-mesenchymal transition. The ability of transcription factors to fulfil their function often depends on their intracellular trafficking between the nucleus and cytoplasm of the cell. The trafficking is regulated by specific sequences, i.e. the nuclear localization signal (NLS) and the nuclear export signal (NES). We performed research on the TCF4 trafficking regulating sequences by mapping and detailed characterization of motifs potentially acting as the NLS or NES. We demonstrate that the bHLH domain of TCF4 contains an NLS that overlaps two NESs. The results of in silico analyses show high conservation of the sequences, especially in the area of the NLS and NESs. This high conservation is not only between mouse and human TCF4, but also between TCF4 and other mammalian E proteins, indicating the importance of these sequences for the functioning of bHLH class I transcription factors.

更新日期：2019-10-30

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